Secondary thioamides and process of preparing them



Patented May 21, 1940 UNITED STATES SECONDARY THI OAMIDES AND PROCESS OF PREPARING THEM William Edward Hanford, Wilmington, net, as-

signor to E. I. du Pont de Nemours & Company, Wilmington, Del., a corporation of Delaware No Drawing. Application September 15, 1938, Serial No. 230,141

11 Claims.

This invention relates to a new process for preparing thioamides, and to certain of the products. The present application is a continuation-in-part of my co-pending application Serial Number 137,149, filed April 15, 1937.

The chief object of the present invention is the development of a satisfactory and economical process for the manufacture of secondary amides of carbothionic acids in which the thiocarbonyl groups are attached to carbon. A further object is to prepare such amides from hydrogen sulfide. Another object is to prepare a groupof thioamides which are themselves new and useful. Other objects will appear from the description which follows.

The objects of the invention are accomplished by reacting hydrogen sulfide with a nitrile and with an amine in which at least one amino group is primary and attached to an aliphatic carbon atom, the reacting groups of polyfunctional reactants being separated by a chain of at least two carbon atoms contiguous therewith and in the case of polyfunctional nitrile reactant preferably by a chain of at least three carbon atoms, continuing the reaction until the evolution of ammonia has substantially ceased. and isolating the carbothionamide formed. The reaction which takes place with a mononitrile and monoamine, the simplest combination, is as follows. The more complex combinations can be deduced therefrom. The Rs represent any monovalent organic radical.

While I do not wish to be bound by any theory, I believe this reaction is a summation of several others which take place (a) the formation, first,

of an amidine between the nitrile and amine, (b) the formation, next, of an unstable hydrogen sulfide addition compound, (c) the decomposition of the latter into ammonia and the carbothionamide By the above process, it is possible to prepare =a wide variety of useful secondary carbothionamides in which the thiocarbonyl group or .groups are attached to carbon. These products either have not previously been known, or, if known, have been obtainable only by complicated and/or expensive synthetic methods. For instance in addition to (1) the simple monomeric carbothionamides from a mononitrile and a monoamine illustrated in the above formula, it is possible to prepare (2) monomeric amides of monocarbothionic acids from mononitriles, and amines having two or more primary aliphatic amino groups, (3) monomeric amides of polycarbothionic acids from primary aliphatic monoamines and most polynitriles, (4) monomeric surface active carbothionamides from the combinations monoamine-mononitrile, monoamine-polynitrile, and mononitrile-polyamine, one of the reactants containing a polar group, (5) thiolactams by the intramolecular reaction of monoamino-mononitriles in which the amine and nitrile groups are separated by a chain of 3, 4, or 5 atoms, (6) polymeric carbothionamides by the intermolecular reaction of monoamino-mononitriles in which the amine and nitrile groups are separated by 5 or more chain atoms, (7) polymeric carbothionamides by reaction of polynitriles with polyamines. Hydrogen sulfide is of course a necessary third reactant in all these combinations.

The present application, in its product aspects, is concerned only with certain of the compounds of types (1) and (2) above. Those of type (3') while a species of my generic invention are specifically the joint invention of Paul L. Salzberg and myself and are described and claimed in our copending application Serial Number 230,144, filed of even date herewith. Those of type (4) are specifically described and claimed in my copending application Serial Number 230,142, filed of even date herewith. The preparation of products of type (5) while a species of my generic invention, is specifically the invention of Paul S. Pinkney and is claimed by him in his copending application Serial Number 199,988, filed April 4, 1938. Those of type (6) are described and claimed generically, and those of type ('7) generiorally and specifically, in my copending application Serial Number 230,143, filed of even date herewith. By reference herein to these several copending applications, the disclosures therein 'on the preparation, properties, and uses of the specific types of carbothionamides with which each'de'al's'are hereby made a part hereof. The present application will describe the generic process invention with the preparation chiefly of type (1)..

In a preferred mode of carrying out the present invention, one mol of nitrile is mixed in a. pressure vessel with about 1.1 mols of amine, and these materials are dissolved in a solvent such as ethyl or "n-butyl alcohol. This solution is cooled externally to 0-5 C, with an ice-salt bath and saturated with hydrogen sulflde. The reaction vessel is then closed and the mixture heated for about 6 to 10 hours at about IOU-150 C., the time of heating varying inversely with the temperature. The vessel is then cooled and opened, the solvent distilled off, and the product isolated by fractional distillation or by crystallization from an appropriate solvent. The yield is good and the product of high purity.

The reaction may also be carried out under atmospheric pressure by passing a steady stream of hydrogen sulfide through the reaction mixture while the latter is heated under reflux to the boiling point of the solvent, the introduction of hydrogen sulfide being continued until substantially no more is absorbed. Under these condi-- tions approximately the same yield is obtained, but more hydrogen sulfide is required. This modification of the process may be desirable, however, when pressure equipment is not available, or when large scale operation with a suitable hydrogen sulfide recover system is contemplated.

The more detailed practice of the invention is illustrated by the following examples, wherein parts given are by weight. There are oi. course many forms of the invention other than these specific embodiments.

EXAMPLE I N-n-dodecylthiobenzamide Twenty-one (21) parts of benzonitrile, 45 parts oi. n-dodecylamine, and 50 parts of ethyl alcohol were placed in a pressure vessel and saturated with hydrogen sulfide, the pressure vessel being cooled in an ice bath. The vessel was sealed and heated for 8 hoursat 100 C., then opened and the alcohol evaporated off. The brown oil which remained was boiled with water for a few minutes to dissolve any thiobenzamide, the oil separated from the hot water and dissolved in low-boiling gasoline, and this solution cooled. Yellow plates of N-n-dodecylthiobenzamide of the formula melting at i i-45 0., were obtained. On analysis, this material was found to contain 10.29% sulfur and 4.68% nitrogen, whereas the calculated amounts for the compound of the formula given are 10.49% and 4.59%, respectively.

EXAMPLE II I N -isobutylthiolauramide Twenty (20) parts of isobutylamine, 36.2 parts of lauronitrile and 50 parts of ethyl alcohol were placed in a pressure vessel immersed in an ice bath, and the solution cooled and then saturated with hydrogen sulfide. The vessel was next sealed and heated for 8 hours at 100 C., after which it was opened and the alcohol evaporated off. The residual oil was dissolved in ether, and the ethereal solution extracted successively with water,

dilute hydrochloric acid, and again with water. The ether was then evaporated oil and the solid dried in vacuo over sulfuric acid. This product,

obtained in about 80% yield, is N-isobutyl thio- -lauramide of the formula C4HaNH-CS-C11H23.

It melts at about 25 C. and had on analysis a sulfur content of 11.32% as compared to a calculated value oi 11.81%.

' EXAMPLE III N-isobutylthiobenzamide Twenty (20) parts of isobutylamine, 30.9 parts of benzonitrile and 50 parts of ethyl alcohol were placed in a pressure vessel'immersed in an ice.

sulfide. for 8 hours at 100 C., after which it was opened and the alcohol evaporated off. The residual brown oil was then boiled with water, separated from the hot water, and dissolved in benzene, and the benzene solution was dried over sodium sulfate. The benzene was next distilled off and the residual oil purified by further distillation in vacuo. This product is N-isobutylthiobenzamide oi the formula It boils at about 168 C./3 mm., is an oil at ordinary temperature, and had on analysis a sulfur content of 16.80% as compared to the calculated value of 16.58%.

ExAMPLE IV N -isobutylthiocaprylamide Thirty (30) parts of isobutylamine, 37.5 parts of caprylonitrile and 25 parts of absolute ethyl alcohol were reacted as in Example III. The N- isobutylthiocaprylamide of the formula which was obtained boils at 172-177 C. at 3 mm. pressure and had on analysis a sulfur content of 14.65% as compared to the calculated value of 14.88%. Substantially the same results were obtained when 80 parts of isobutylamine and 125 parts of caprylonitrile were reacted in the same manner in the presence of 300 parts of ethyl alcohol.

EXAMPLE V N-n-dodecylthiobenzamide It has the same properties as the product of Example I.

EXAMPLE VI 1 ,6-bis- (thioacetylamino) hexane A solution of 13.3 parts of hexamethylenediamine and 8.2 parts of acetonitrile in 80 parts of ethanol in a pressure vessel was saturated at 0 C. with hydrogen sulfide. The pressure vessel was sealed, heated at 100 C. for eight hours, cooled, opened, and the clear yellow solution poured into 300 parts of cold water. precipitate thus obtained was collected on a filter, washed with cold water, and air-dried. This compound is 1,6-bis-(thioacetylamino)hexane of the formula CHIlCS-NH(CH2)6NH CS CH3. After crystallization from ethanol, it melts at 99-100 C. and had on analysis a sulfur contentof 26.94% as compared to the calculated value of 27.59%.

EXAMPLE VII N,N'-dicyclohemyldithioadipamide A solution or 26.8 parts of cyclohexylamine and The white crystalline The vessel was then sealed. and heated l0.8 parts adiponitriie in 90 parts of ethanol was placed in an autoclave, cooled to about 5 C. and saturated with hydrogen sulfide. The autoclave was then sealed and heated with stirring at 100-110 C. for eight hours, after which it was cooled, opened, and the contents poured into twice their volume of cold water. The waterif the latter, monoor polycyclic; saturated or unsaturated; and substituted or not by groups other than those taking part in the reaction.

ess include the following:

insoluble material which separated wastaken up with ether, the ether evaporated off, the oily residue dissolved in methanol, water added until the solution became turbid and the mixture then Mflnobflfllc fields Poiy uic acids cooled and stirred. N,N'-dicyclohexyidithioa- Benzonitrlle Suocinonitrlle dipamide of the formula hummus Adponmue gsp ryl i nhtrile (sfibfiollltilgfi 08 on 8 11 I01) 6 C8H11 NH (CH2) CS NH d-aminoca'pronitrile fi-methylglutaronitrlle i 1(zleoiiiiti'iileu 133119111111tlnilonitrilo separated as a white crystalline productwhich gg i ggggg gflgg ggg was filtered off and purified by crystallization gl rgg o rinitrfle g ggi true from methanol. The pure product melts at P8 mitonit fle gkemplmeiogm, 168-168.5 C. It had on analysis a sulfur content g t e zggi i r l l g Dlphlgrlio aeitulitrilehs which checked with the calculated value within mgolleonme gll g g experimental error. 9- 011011 e -M i u The following additional carbothionamides gl afiigiggfi iififi" have been prepared by the same general techfl-nflvhtmmitrfle nique of the above examples:

Sulfur analysis Compound Physical constants Yield Oslo. Found Per cent Percent Per cent N-benzylthiobenzamide.-. M. P. 7s-s0 0 12.5 14.0 13.0 N-n-octylthiobenzamide... B. P. 196-197/2 mm. 57.0 12.8 11. 6 N-isobutylthioolesmide.... B. P. 236-238/4 mun... 51. 0 9.0 8.0 N,N-di-n-octyiditbioadip- M. P. 1l3-114C 85.0 15.2 16.4

amide.

. Amines In this process, a temperature range of to 250 C. may in general be used, and temperatures Mono'ammes Myammes above 250 C. are sometimes applicable. The process may be carried out under atmospheric or Hommethylenediamine dn t Decamethylenediamine superatmospheric pressures. Inert uen s Ethylenedmmme Trlniethvlenediamlne which are solvents for the reactants and solvents or non-solvents for the products will generally be employed to advantage. Suitable diluents include ethanol, butanol, pentanols, dioxan, acetone, toluene, xylene, benzene, and -methoxyethanol. The ratios of reactants given in the examples are not limiting. A slight excess of amine over that stoichiometrically required to react with the nitrile is preferable, but the process can also be operated with excess nitrile. A slight excess of hydrogen sulfide is preferably used in all cases.

By the present process, it is possible to react any monoor polynitrile with any monoor polyamine having at least one amino group which is primary and attached to an aliphatic carbon, (1. e., a carbon which is not a part of an aromatic ring) and to react any primary monoaminomononitrile (the amino group being attached to an aliphatic carbon) with itself-provided the reacting groups of those of these reagents that are polyvalent are separated by a chain of at least two carbon atoms, and in the case of a poly functional nitrile reactant preferably by a chain of at least three carbon atoms. The reactants may therefore be aromatic, aliphatic (including alicyclic), or heterocyclic; acyclic or cyclic, and

Tetrame-hylenediamine a-inethy'tetramethylenodlamine Trigli/coamine p ilarniiodigmlriropyl ether ro one he 2,3- iimlnobutene 1, clohe lenediamine -xy ylened ine exedeeamethylenediamlne +R-NHI+HQS 0 CN 8 os-nn-a NR CN (3 NH (Iminotli'ioplitliallmide) in many inventively new products.

R. is any organic radical containing an aliphatic carbon adjacent to the amino group. Because of the peculiar behavior of polynltriles in which the nitrile groups are separated by chains of only two carbons, Iprefer to employ, in making amides of polycarbothionic acids, polynitriles in which the nitriles are separated by longer chains, 1. e., chains of three or more atoms. It is necessary to do this when a polymeric carbothionamide is desired.

Certain amines and nltriles are excluded from the scope of the invention as above defined for reasons, of inoperativeness, inavailability of the reactant, etc., e. g., oxalonitrile, malononitrile, methylene diamine, etc.' As indicated immediately above, polyfunctlonal nitrilereactions preferably have the nitrile group separated from the other reacting group by a chain of at least thre carbon atoms.

In place of the pure nitriles and amines, there may be used any desired mixtures thereof, and mixtures of carbothionamides will be obtained. For example, I may employ the mixture of nitriles obtained by the catalytic dehydration of coconut oil acids in the presence of ammonia, in which case the products will be composed of about 2% thiocaproamides, 9% thiocaprylamides, 10% thiocapramides, 45% thiolauramides, 20% thiomyristamides, 5% thiopalmitamides, 9% thiostearamides, and traces of thiooleamides and thioarachidamides. These amides, of course, are all substituted on the amido nitrogen by the radical of the amine used. A

The process of the present invention results Of these, the present application is concerned with certain of the compounds of types (1) and (2) hereinbefore referred to, which may be considered as derived from monocarbothionic acids. They may be defined as secondary monocarbothionamides in which the thioamide nitrogen substituent has at least four carbons, and is united to the amide nitrogen by aliphatic carbon. The thioamide nitrogen substituent is the substituent on the thioamido nitrogen, i. e., the radical obtained from the parent amine by subtracting the primary amino group or groups. The products may be comprehensively formulated as in which 1'1. is the residue of a monocarbothionic acid, and is joined to the thiocarbonyl group through carbon, R is the thioamido nitrogen substituent as just defined, and a: is the valence 01 R. Preferably R is a saturated hydrocarbon radical. When :c =1, the formula reduces to i. e., to the formula forproducts obtained from monoamines.

The secondary amides of monocarbothionic acids and of saturated hydrocarbon monoamines of at least four carbon atoms, of which N-isobutylthlobenzamide and N-isobutylthiocaprylamide are typical, are stable high-boiling oils or lowmelting solids which have practically no odor, a property which is a decided advantage when the compounds are to be used as insecticides or as metal deactivators for gasoline. The fact that they are in most cases liquids or low-melting solids facilitates their solubility in organic solvents. They are strikingly different in these respects from i -dicarbethoxy-N-allylthioacetamide and the diamide of u,a-dicarboxy-N-allylthioacetamlde, which are high-melting, easily decomposed solids and hence of little practical use, and from N-allylthioacetamide and N-allylthiopropionamide, which are liquids that readily decompose and possess a garlic-like'odor.

The secondary monocarbothionamides with which the present application is concerned as products are useful as metal deactivators for gasoline, as insecticides, and as plasticizers in compositions for moistureproofing regenerated cellulose sheeting.

The above description and examples are intended to be illustrative only. Any modification of or variation therefrom which conforms to the spirit of the invention is intended to be included within the scope of the claims.

I claim:

1. Process for preparing thioamides which comprises reacting hydrogen sulfide with a nitrile and with an amine having at least one primary amino group attached to an aliphatic carbon atom, the reacting groups being separated by a chain of at least two contiguous carbon atoms when the reactants are polyfunctional.

2. Process for preparing thioamides which comprises reacting hydrogen sulfide with a nitrile and with an amine having at least one primary amino group attached to an aliphatic carbon atom, the reacting groups being separated by a chain of at least two contiguous carbon atoms when the reactants are polyfunctional and by a chain of at least three carbon atoms in the case of a polyfunctional nitrile reactant.

3. Process for preparing thioamides which comprises reacting hydrogen sulfide with a mononitrile and with an amine having at least one primary amino group attached to an aliphatic carbon atom, and separated by a chain of at least two carbons from any other reacting group.

4. Process for preparing thioamides which comprises reacting hydrogen sulfide with a mononi trile and with a primary saturated aliphatic hydrocarbon monoamine of at least four carbon atoms.

5. Process as set forth in claim 2, which is carried out in the presence of an inert solvent for the reactants.

6. Process as set forth in claim 2, the temperature being in the range of from to 250 C.

7. Process as set forth in claim 2, in which the reaction is carried out in an inert solvent at a temperature of from 50 to 250 C., and is continued until the evolution of ammonia has substantially ceased.

8. A secondary monocarbothionamide in which the thioamido nitrogen substituent has at least four carbon atoms and is united to said nitrogen by an aliphatic carbon atom.

acid and is Joined to the thiocarbonyl group through carbon, R is a radical of at least four carbons which is united to the thioamido nitro' gen by aliphatic carbon, of R. I

10. A thioamide of the formula and a: is the valence in which R is the residue of a monocarbothionic acid and is joined to the thiocarbonyl group through carbon, and, R is a radical of at least in which R is the residue of a monocarbothionic four carbons which is united to the thioamido acid and is joined to the thiocarbonyl group nitrogen atom by an aliphatic carbon atom. through carbon, and R is a saturated aliphatic 11. A thioamide of the formula hydrocarbon radical of at least four carbon atoms.

R CS-NH-R WILLIAM EDWARD HANFORD. 

